PHILADELPHIA — Patients with advanced prostate cancer who had pre-existing cardiovascular disease had higher risk of mortality in the six months after starting abiraterone acetate (Zytiga) treatment compared with those who had no pre-existing cardiovascular disease, according to data presented during a media preview of the AACR Annual Meeting 2019, which will be held March 29–April 3, in Atlanta.

“Patients with a history of significant cardiovascular disease or uncontrolled hypertension are almost always excluded from clinical trials of abiraterone acetate,” said Grace Lu-Yao, PhD, MPH, associate director for Population Science at the Sidney Kimmel Cancer Center at Jefferson in Philadelphia. “However, in the real-world setting, these conditions are very common among men with prostate cancer.

“Our data show that patients who have pre-existing cardiovascular disease experienced higher mortality after receiving abiraterone acetate compared with those who do not and the bulk of the survival differences occurred in the first six months,” continued Lu-Yao, who is also vice chair and professor in the Department of Medical Oncology at the Sidney Kimmel Medical College. “These data also provide rationale for relaxing clinical trial exclusion criteria to ensure greater generalizability of trial results to the real world.

“It is very important that patients with advanced prostate cancer understand that the outcomes of abiraterone acetate treatment observed in clinical trials may not apply to patients in the real world, especially those not meeting the eligibility criteria of the clinical trials,” Lu-Yao said.

To study real-world clinical outcomes among patients treated with abiraterone acetate for advanced prostate cancer, Lu-Yao and colleagues obtained population-based data from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked data resource and identified 2,845 patients who were diagnosed with prostate cancer between Jan. 1, 1991, and Dec. 31, 2013, and treated with abiraterone acetate between 2011 and 2014.

The researchers investigated the outcomes of patients with pre-existing significant cardiovascular disease to fill a major knowledge gap resulting from restricted exclusion criteria in existing clinical trials. They found that 1,924 (67.6 percent) patients had at least one serious cardiovascular condition (for example, acute myocardial infarction, atrial fibrillation, congestive heart failure, stroke, and ischemic heart disease) before starting treatment with abiraterone acetate. These patients had a significantly higher all-cause mortality in the six months after starting abiraterone acetate compared with those who had no pre-existing cardiovascular disease; the crude risk of overall mortality by six months ranged from 21.4 percent to 25.6 percent depending on the type of pre-existing cardiovascular condition, versus 15.8 percent for those with no pre-existing cardiovascular disease.

To assess the impact of abiraterone acetate treatment on health care utilization, the researchers analyzed the hospitalization rate in the six months before and after abiraterone acetate and found a substantial increase in hospitalization rate after the treatment. Among patients without chemotherapy, the hospitalization rate increased by 53 percent among those who had no pre-existing cardiovascular disease. Among those with pre-existing cardiovascular disease, it ranged from a 34 percent increase among those with atrial fibrillation to 55 percent increase among those with acute myocardial infarction.

“The increased post-treatment hospitalization rate shows that there is risk associated with abiraterone acetate for all patients,” said Lu-Yao.

Abiraterone acetate was first approved by the U.S. Food and Drug Administration in April 2011 for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. In February 2018, it was approved for uses in combination with prednisone for metastatic high-risk castration-sensitive prostate cancer.

“As we move abiraterone acetate treatment to patients with earlier stages of the disease and longer life expectancy, it is important to evaluate whether the benefits outweigh the risks based on the health status of the patients and to ensure that patients are carefully monitored for potential side effects,” said Lu-Yao.

According to Lu-Yao, the main limitation of the study is that the researchers could not address treatment efficacy among these vulnerable patients given the study’s retrospective nature, the presence of confounders such as variable disease states, and the inability to quantify expected survival without control groups. “We also could not directly compare our study population against the inclusion/exclusion criteria of the pivotal abiraterone acetate trials due to insufficient clinical information from the SEER database,” said Lu-Yao. “In addition, the cardiovascular conditions were derived from the Medicare files and misclassification might occur.”

This study was funded by a Pennsylvania CURE Program award and the National Cancer Institute. Lu-Yao has no direct conflicts to declare except that her spouse, who has no involvement with this study, is an officer of Sun Pharmaceutical Industries Inc.